Prednisolone impairs trabecular bone score changes in adolescents with 21-hydroxylase deficiency

Individuals with 21-hydroxylase deficiency (21OHD) require lifelong glucocorticoid (GC) therapy, which increases their risk of fragility fractures. However, fractures in GC-treated individuals can occur at normal bone mineral density (BMD) levels, suggesting an alteration in the bone microarchitecture.

To evaluate trabecular bone microarchitecture and its changes in adolescents with 21OHD.

We enrolled 38 adolescents with 21OHD for whom complete clinical data and baseline and follow-up lumbar spine BMD (LSBMD) measurements were available. The mean duration was 1.5±0.6 years. Trabecular bone score (TBS), an indirect measurement of bone microarchitecture, was analyzed using iNsight software version 3.0. Impaired BMD and TBS were defined as z scores ≤ -1.5.

At baseline, participants (55% female; 68% salt- wasting type; mean age, 15.2±3.8 years; bone age, 17.5± 2.8 years; mean GC dose, 18.5±6.5 mg/m2/day) had the prevalence of impaired BMD and TBS of 5% and 18%, respectively. During follow-up, adolescents with 21OHD receiving prednisolone showed a lower annual percentage change in TBS than those who received hydrocortisone (P=0.028). A stepwise regression analysis showed that body mass index percentile (P<0.001) and testosterone concentration (P=0.002) were independent positive predictors of the baseline TBS z score, whereas prednisolone use was the only negative predictor of the annual percentage change in TBS (P=0.002).

Adolescents with 21OHD have a high prevalence of impaired bone microarchitecture. Furthermore, prednisolone therapy is associated with impaired bone microarchitecture development, suggesting that hydrocortisone may better preserve bone microarchitecture and should be considered the first-line treatment for this population.